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Amebiasis
Amebiasis is infection with
Entamoeba histolytica.
This organism can cause:
Asymptomatic intestinal infection.
Mild to moderate colitis.
Severe intestinal infection (dysentery).
Ameboma (a tumor-like mass in the
intestines in amebiasis which results
in a large local lesion of the bowel ).
Liver abscess and other extraintestinal infection.
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Ameboma
Treatment of Specific Forms of Amebiasis
Asymptomatic Intestinal Infection
Asymptomatic carriers are treated with a luminal amebicide.
Standard luminal amebicides are:
Diloxanide furoate, Iodoquinol, and Paromomycin.
Therapy with a luminal amebicide is also required in the
treatment of all other forms of amebiasis.
Amebic Colitis
Metronidazole + a luminal amebicide
is the treatment of choice.
Tetracyclines and erythromycin are
alternative drugs for moderate colitis but Amebic Colitis
are not effective against extraintestinal disease.
Dehydroemetine or emetine can also be used, but are
best avoided because of toxicity.
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Metronidazole
Drug of choice in the treatment of
extraluminal amebiasis.
It kills trophozoites but not
cysts of E histolytica and
effectively eradicates intestinal
& extraintestinal tissue infections.
Tinidazole
Similar activity
& better toxicity profile than metronidazole.
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cysts of E histolytica
Pharmacokinetics & Mechanism of Action
Oral metronidazole and tinidazole are readily
absorbed.The half-life: Metronidazole 7.5 hours
Tinidazole 12–14 hours.
The nitro group of metronidazole is reduced in
anaerobic bacteria and sensitive protozoans.
It inhibits nucleic acid synthesis by disrupting the DNA
of microbial cells. This function only occurs
when metronidazole is partially reduced, and
because this reduction usually happens only in
anaerobic cells, it has relatively little effect upon
human cells or aerobic bacteria.
The mechanism of tinidazole is the same
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Clinical Uses
Amebiasis
Metronidazole or tinidazole
The drug of choice in the treatment of all tissue infections with E
histolytica. (hepatic abscess; intestinal wall/ extraintestinal infections)
Not effective against luminal parasites and so must be used •
with a luminal amebicide to ensure eradication of the
infection. kills trophozoites but not cysts
Giardiasis
Metronidazole is the treatment of choice
Efficacy after a single treatment is about 90%
Tinidazole is equally effective.
Trichomoniasis
Metronidazole is the treatment of choice.
5 A single dose of 2 g is effective.
Trichomonas vaginalis
Adverse Effects & Cautions
Common:
Nausea, headache, dry mouth, metallic taste.
Infrequent adverse effects:
vomiting, diarrhea, insomnia, weakness, dizziness,
thrush, rash, dysuria, dark urine, vertigo,
paresthesias, and neutropenia.
Rare:
Pancreatitis and severe central nervous system toxicity
(ataxia, encephalopathy, seizures)
Metronidazole has a disulfiram -like effect.
Tinidazole is better tolerated.
Metronidazole is best avoided in pregnant or nursing
women, although congenital abnormalities have not
clearly been associated with use in humans.
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Iodoquinol
Luminal amebicide, but not against
intestinal wall or extraintestinal trophozoites.
90% is excreted in the feces.
Infrequent adverse effects:
Diarrhea , anorexia, nausea, vomiting, abdominal pain,
headache, rash, and pruritus.
Taken with meals to limit gastrointestinal toxicity.
Used with caution in patients with optic neuropathy,
renal or thyroid disease, or nonamebic hepatic
disease.
Should be discontinued if it produces persistent diarrhea
or signs of iodine toxicity (dermatitis, urticaria, pruritus,
fever).
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Diloxanide Furoate
Drug of choice for
asymptomatic luminal infections.
Not active against tissue trophozoites.
In the gut, it splits into diloxanide
and furoic acid; about 90% of the
diloxanide is rapidly absorbed.
The unabsorbed diloxanide is the active antiamebic
The mechanism of action is unknown.
Used with a tissue amebicide, usually metronidazole,
to treat serious intestinal & extraintestinal infections.
Adverse effects:
Flatulence is common, nausea & abdominal cramps
are infrequent & rashes are rare.
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Paromomycin Sulfate
Aminoglycoside antibiotic that is not absorbed from
the gastrointestinal tract.
It is used only as a luminal amebicide and has no
effect against extraintestinal amebic infections.
Adverse effects
Occasional abdominal distress & diarrhea.
Parenteral paromomycin is now used
to treat visceral leishmaniasis.
a sand fly
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Post-kala-azar dermal leishmaniasis ,
a complication of visceral leishmaniasis.
Emetine & Dehydroemetine
Emetine, an alkaloid derived from ipecac.
Dehydroemetine, a synthetic analog.
Effective against tissue trophozoites of E histolytica,
Their use is limited to severe amebiasis when
metronidazole cannot be used.
Used for the minimum period needed to relieve severe
symptoms (3–5 days) and should be administered
S.C. (preferred) or I.M.
Adverse effects
Pain, tenderness, and sterile abscesses at the
injection site; diarrhea, nausea, and vomiting;
muscle weakness and discomfort.
Serious toxicities include cardiac arrhythmias,
heart failure, and hypotension.
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ANTHELMINTIC DRUGS
Albendazole
broad spectrum. drug of choice for hydatid disease &
cystecercosis.
also used for (intestinal nematodes) pinworm,
hookworm
Mechanism of action:
inhibits microtubule synthesis in nematodes that
irreversibly impairs glucose uptake, intestinal
parasites are immobilized and die slowly.
orally , absorbed erratically, increased with fatty meal
metabolized in the liver to active metabolite
albendazole sulphoxide , half life of 8-12 hours
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used on empty stomach for intraluminal parasites but
with fatty meal when against tissue parasites.
2. Hydated diseases: drug of choice ,400 mg twice with
meals for 1 month
3. Neurocysticercosis: used along with cotricosteroid to
decrease the inflammation caused by dying organism
Adverse effects:
short term: use no significant adverse effects.
long term use : abdominal distress, headache ,fever ,
fatigue, alopecia , increased liver enzymes ,
pancytopenia. (low level of all blood cells produced
by the bone marrow ).
Not given during pregnancy & in hypersensitive people.
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Mebendazole
has wider spectrum and is more safe than albendazole
Mechanism of action:
inhibits microtubule synthesis, irreversibly impairs glucose
uptake. Intestinal parasites are immobilized & die slowly.
kills hook worm, pin worm , ascariasis and trichuriasis.
Less than 10% of drug is absorbed
Absorption increases with fatty meal.converted to inactive
metabolites rapidly in liver. half life of 2-6 hours
Given orally before or after meals, tablets should be
chewed before swallowing.
Adverse effects and precautions:
short term therapy. Mild GI disturbance.
high dose Hypersensitivity reactions, agranulocytosis (rare)
, alopecia ,elevation of liver enzymes .
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caution under 2ys of age may cause convulsion.
Pyrantel Pamoate
Broad-spectrum antihelminthic, highly effective for
pinworm, ascaris & Trichostrongylus orientalis
infections and moderately effective against hookworm.
A neuromuscular blocker, causes paralysis of worms,
which is followed by expulsion.
Effective in intestinal tract, not in the tissues or the ova
Given orally once with or without food.
For pinworm, the dose is repeated in 2 weeks.
For ascariasis, a single dose be repeated if eggs are
found 2 weeks after treatment.
For hookworm, a single dose is effective against light
infections. In heavy infections, a 3-day course.
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A course of treatment can be repeated in 2 weeks.
Piperazine
Only recommended for the treatment of ascariasis.
Causes paralysis of ascaris by blocking ACh at the
myoneural junction.
live worms are expelled by normal peristalsis.
readily absorbed orally and excreted unchanged in urine.
Given orally once daily for 2 days.
For heavy infections treatment is repeated after 1 wk.
Adverse effects: generally mild (5–30%)
nausea, vomiting, diarrhea, abdominal pain, dizziness, &
headache.
Neurotoxicity & allergic reactions are rare.
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Niclosamide
Used for the treatment of most tapeworm infections.
Niclosamide is a salicylamide derivative.
Minimally absorbed from the GIT.
Adult worms (but not ova) are rapidly killed, due to
inhibition of oxidative phosphorylation or stimulation
of ATPase activity.
Clinical Uses
2 g once, given in the morning on an empty stomach.
The tablets must be chewed thoroughly and then
swallowed with water. Purgative needed.
Adverse effects:
Mild ,infrequent and transitory GI disturbance
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Diethylcarbamazine Citrate
Drug of choice for filariasis, Loa loa &
tropical eosinophillia.
Rapidly absorbed from gut, half life of 2-3 hours ,
excreted in urine unchanged.
Mechanism of action:
immobilizes microfilariae and alters its surface
structure ,making them susceptible to destruction by
host defense mechanism
Microfiliariae are rapidly killed .adult worms are killed
slowly requiring several course of treatment
The mode of action against adult worms is unknown.
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Adverse Reactions
generally mild and transient, include headache, malaise,
anorexia, weakness, nausea, vomiting, and dizziness.
Adverse effects also occur as a result of the release of
proteins from dying microfilariae or adult worms.
Reactions include fever, malaise, papular rash,
headache, gastrointestinal symptoms, cough, chest
pain, and muscle or joint pain.
Leukocytosis is common (white blood cell count above
the normal range in the blood).
Eosinophilia (abnormally high amounts of eosinophils).
Proteinuria may also occur.
Caution when using diethylcarbamazine in patients with
hypertension or renal disease.
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Doxycycline
Has macrofilaricidal activity against Wuchereria
bancrofti (lymphatic filariasis), and better activity than
any other available drug against adult worms.
Active also against onchocerciasis
(river blindness)
Doxycycline acts indirectly, by killing Wolbachia, an
intracellular bacterial symbiont of filarial parasites.
It may be used for filariasis, both for treatment of active
disease and in mass chemotherapy campaigns.
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Ivermectin
Drug of choice for the treatment of onchocerciasis
(river blindness) and for strongyloidiasis.
Strongyloidiasis:
A GABA agonists Paralyzes nematodes, causing a flaccid
paralysis in the worm. Does not cross the blood brain
barrier in humans (therefore little CNS effects). .
Onchocerciasis:
Microfilaricidal. It does not kill adult worms but blocks the
release of microfilariae.
After a single dose, microfilariae in the skin diminish rapidly
within 2–3 days .
Microfilariae in the anterior chamber of the eye decrease
slowly over months. Repeated doses have a low
macrofilaricidal action and permanently reduce microfilarial
production.
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Adverse Reactions:
In strongyloidiasis:
fatigue, dizziness, nausea, vomiting, abdominal pain,
and rashes.
In onchocerciasis
Occurs in 5–30% ,generally mild due to the killing of
microfilariae.
A more intense reaction in 1–3%
A severe reaction in 0.1%, including high fever,
hypotension, and bronchospasm.
Swellings and abscesses occasionally occur at 1–3
weeks at sites of adult worms.
Corneal opacities & eye lesions may develop several
days after treatment.
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Bithionol
the drug of choice in the treatment of sheep liver fluke
(Fasciola hepatica) and the second drug of choice in lung
fluke (Paragonimus westermani ).
Mechanism of action:
Unknown, bithionol may work may uncoupling oxidative
phosphorylation, thus reducing the production of ATP in the
helminthes.
Adverse Reactions:
generally mild (40% of patients) and include:
diarrhea, abdominal cramps, anorexia, nausea, vomiting,
dizziness, and headache.
Skin rashes may occur, a reaction to antigens released from
dying
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Praziquantel
Effective in schistosome infections of all species &
most other trematode & cestode infections, including
cysticercosis.
safe and effective as a single oral dose.
Useful in mass treatment of several infections.
Plasma concentrations of praziquantel increase when
the drug is taken with a high-carbohydrate meal.
It increases the permeability of cell membranes to
calcium, resulting in paralysis,
dislodgement, and death.
Mild and transient adverse effects,
except for Neurocysticercosis
due to inflammatory reactions
around dying parasites.
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Metrifonate
Safe, low-cost alternative drug for Schistosoma
haematobium infections.
Not active against S mansoni or S japonicum.
Organophosphate cholinesterase inhibitor temporarily
paralyzes the adult worms, resulting in their shift from
the bladder venous plexus to small arterioles of the
lungs, where they are trapped, encased by the immune
system, and die.
Given three times orally at 14-day
intervals.
A prophylactic agent when given
monthly to children
Used in mass treatment programs.
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Oxamniquine
Alternative to praziquantel for the
treatment of S mansoni infections.
Used extensively for mass treatment.
Not effective against S haematobium or S japonicum.
Active against both mature and immature stages.
The mechanism of action is unknown.
Contraction and paralysis of the worms results in
detachment from terminal venules in the mesentery and
transit to the liver, where many die.
Surviving females return to the mesenteric vessels but
cease to lay eggs.
In mixed schistosome infections, it has been used in
combination with metrifonate.
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